title: Development and validation of a liquid chromatography-tandem mass spectrometry method for the determination of zofenopril and its active metabolite zofenoprilat in human plasma.
abstract: A novel, sensitive and rapid liquid chromatographic-electrospray ionization mass spectrometric method was developed and validated for the determination of zofenopril and its active metabolite zofenoprilat in human plasma. The method was based on a single extraction step using methyl tert-butyl ether and did not require chemical derivatization. The chromatographic conditions were optimized; separation was performed on a phenyl-hexyl column (5μm, 250mm×4.6mm i.d.) with a mobile phase consisting of a solution of methanol and water (95:5, v/v) that also contained 0.1% of formic acid. A flow rate of 1.0mL/min was used. Zofenopril, zofenoprilat and the internal standard (IS) fosinopril sodium were measured using an electrospray ion source in a positive reaction monitoring mode. Linear calibration curves were generated for zofenopril concentrations between 0.1052 and 1052ng/mL and for zofenoprilat concentrations between 0.2508 and 2508ng/mL. In both cases, the coefficients of determination were greater than 0.995. The extraction recovery for zofenopril was 93.5% on average. It was 92.5% for zofenoprilat. The inter- and intra-batch precision and accuracy for both zofenopril and zofenoprilat were higher than 14%. The method was applied to measure the concentrations of zofenopril and zofenoprilat in plasma samples.
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Fang
authors.initials: F
authors.lastname: Yan
authors.forename: Bin
authors.initials: B
authors.lastname: Di
authors.forename: Fang
authors.initials: F
authors.lastname: Feng
authors.forename: Linjun
authors.initials: L
authors.lastname: You
authors.forename: Lili
authors.initials: L
authors.lastname: Huang
authors.forename: Juan
authors.initials: J
authors.lastname: Lu
mesh_terms: D002138:Calibration; D002216:Captopril / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D007202:Indicators and Reagents; D057230:Limit of Detection; D015394:Molecular Structure; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000295:instrumentation / Q000379:methods*
chemical_list: D007202:Indicators and Reagents; C044958:zofenopril; C065520:zofenoprilate; D002216:Captopril